IL-4/IL-13 Signaling Regulation and Monoclonal Antibody Therapy in Chronic Rhinosinusitis with Nasal Polyps

Tao Lin; Yingying Zhang; Dongling Lian; Zhiqing Ma

doi:10.54097/g17g1485

Authors

Tao Lin
Yingying Zhang
Dongling Lian
Zhiqing Ma

DOI:

https://doi.org/10.54097/g17g1485

Keywords:

Chronic Rhinosinusitis with Nasal Polyps (CRSwNP), Type 2 Inflammation, IL-4/IL-13 Signaling, Monoclonal Antibodies, Dupilumab, Personalized Treatment

Abstract

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a prevalent inflammatory disorder characterized by nasal obstruction, rhinorrhea, hyposmia/anosmia, and facial pain. It is driven by type 2 (T2) inflammation, primarily mediated by IL-4, IL-13, and IL-5. Current treatments, including corticosteroids and surgery, often fail to address the underlying T2 inflammation and have limitations in efficacy and safety. Recent advances in monoclonal antibody therapies targeting IL-4/IL-13 signaling, such as dupilumab, have shown significant efficacy in reducing nasal polyp burden, improving olfactory function, and enhancing quality of life. However, challenges remain due to disease heterogeneity and the need for personalized treatment strategies. Future research should focus on leveraging multidimensional technologies to dissect disease heterogeneity, developing novel therapeutic agents, and conducting head-to-head clinical trials to refine treatment selection.

Downloads

Download data is not yet available.

References

[1] Peters AT, Tan BK, Stevens WW. Consultation for Chronic Rhinosinusitis With Nasal Polyps and Asthma: Clinical Presentation, Diagnostic Workup, and Treatment Options. J Allergy Clin Immunol Pract. 2024;12(11):2898-2905. doi:10. 1016/j.jaip.2024.07.019.

[2] Stevens WW, Kato A. Group 2 innate lymphoid cells in nasal polyposis. Ann Allergy Asthma Immunol. 2021;126(2):110-117. doi: 10.1016/j.anai.2020.08.001.

[3] Bachert C, Hicks A, Gane S, et al. The interleukin-4/interleukin-13 pathway in type 2 inflammation in chronic rhinosinusitis with nasal polyps. Front Immunol. 2024;15:1356298. Published 2024 Apr 16. doi:10. 3389/ fimmu.2024.1356298.

[4] Fieux M, Carsuzaa F, Bellanger Y, et al. Dupilumab prevents nasal epithelial function alteration by IL-4 in vitro: Evidence for its efficacy. Int Forum Allergy Rhinol. 2024;14(8):1337-1349. doi:10.1002/alr.23343.

[5] Saraswathula A, Liu MM, Kulaga H, Lane AP. Chronic interleukin-13 expression in mouse olfactory mucosa results in regional aneuronal epithelium. Int Forum Allergy Rhinol. 2023;13(3):230-241. doi:10.1002/alr.23073.

[6] Haloob N, Karamali K, Hopkins C. The Role of Biologics in the Treatment of Chronic Rhinosinusitis. BioDrugs. 2023;37 (4):477-487. doi:10.1007/s40259-023-00602-9.

[7] Minskaia E, Maimaris J, Jenkins P, et al. Autosomal Dominant STAT6 Gain of Function Causes Severe Atopy Associated with Lymphoma. J Clin Immunol. 2023;43(7):1611-1622. doi:10. 1007/s10875-023-01530-7.

[8] Akdis CA, Arkwright PD, Brüggen MC, et al. Type 2 immunity in the skin and lungs. Allergy. 2020;75(7):1582-1605. doi: 10.1 111/ all.14318.

[9] Pelaia C, Pelaia G, Crimi C, et al. Biological Therapy of Severe Asthma with Dupilumab, a Dual Receptor Antagonist of Interleukins 4 and 13. Vaccines (Basel). 2022;10(6):974. Published 2022 Jun 19. doi:10.3390/vaccines10060974.

[10] Tay HL, Foster PS. Biologics or immunotherapeutics for asthma?. Pharmacol Res. 2020;158:104782. doi:10.1016/j. phrs. 2020.104782.

[11] Hoy SM. Dupilumab: A Review in Chronic Rhinosinusitis with Nasal Polyps. Drugs. 2020;80(7):711-717. doi:10.1007/ s402 65-020-01298-9.

[12] Hopkins C, Wagenmann M, Bachert C, et al. Efficacy of dupilumab in patients with a history of prior sinus surgery for chronic rhinosinusitis with nasal polyps. Int Forum Allergy Rhinol. 2021;11(7):1087-1101. doi:10.1002/alr.22780.

[13] Ferri S, Montagna C, Casini M, et al. Sleep quality burden in chronic rhinosinusitis with nasal polyps and its modulation by dupilumab. Ann Allergy Asthma Immunol. 2024;132(1):69-75. doi: 10.1016/j.anai.2023.08.594.

[14] Kychygina A, Cassagne M, Tauber M, et al. Dupilumab-Associated Adverse Events During Treatment of Allergic Diseases. Clin Rev Allergy Immunol. 2022;62(3):519-533. doi:10.1007/s12016-022-08934-0.

[15] Fujieda S, Matsune S, Takeno S, et al. Dupilumab efficacy in chronic rhinosinusitis with nasal polyps from SINUS-52 is unaffected by eosinophilic status. Allergy. 2022;77(1):186-196. doi:10.1111/all.14906.

[16] Yang B, Wilkie H, Das M, et al. The IL-4Rα Q576R polymorphism is associated with increased severity of atopic dermatitis and exaggerates allergic skin inflammation in mice. J Allergy Clin Immunol. 2023;151(5):1296-1306.e7. doi:10. 1016/ j.jaci.2023.01.011.

[17] Laidlaw TM, Bachert C, Amin N, et al. Dupilumab improves upper and lower airway disease control in chronic rhinosinusitis with nasal polyps and asthma. Ann Allergy Asthma Immunol. 2021;126(5):584-592.e1. doi:10.1016/j. anai.2021.01.012.

[18] Paoletti, G., Paoletti, G., Casini, M.,et al. Very rapid improvement of extended nitric oxide parameters, associated with clinical and functional betterment, in patients with chronic rhinosinusitis with nasal polyps (CRSwNP) treated with Dupilumab. Journal of investigational allergology & clinical immunology.doi:10.18176/jiaci.0851.

[19] Ryser FS, Yalamanoglu A, Valaperti A, et al. Dupilumab-induced eosinophilia in patients with diffuse type 2 chronic rhinosinusitis. Allergy. 2023;78(10):2712-2723. doi:10. 1111/ all. 15844.

[20] Guo CL, Liu FF, Wang DY, Liu Z. Type 2 Biomarkers for the Indication and Response to Biologics in CRSwNP. Curr Allergy Asthma Rep.2023;23(12):703-713. doi:10.1007/ s11882-023-01114-w.

[21] Ren X, Wang Z. High chemokine ligand 11 levels in nasal lavage fluid: A potential predictor of and therapeutic target for murine eosinophilic chronic rhinosinusitis. Life Sci. 2021; 271: 119218. doi:10.1016/j.lfs.2021.119218.

[22] Abdu S, Xia J, Yuan H, et al. IL-25 Enhances B Cell Responses in Type 2 Inflammation Through IL-17RB Receptor. Allergy. Published online January 19, 2025. doi:10.1111/all.16472.

[23] Gayvert K, Desrosiers M, Laidlaw TM, et al. Nasal brushing molecular endotyping distinguishes patients with chronic rhinosinusitis with nasal polyps with better response to dupilumab. J Allergy Clin Immunol. 2024;154(3):619-630. doi: 10.1016/j.jaci.2024.05.030.

[24] Rodriguez-Iglesias M, Calvo-Henríquez C, Martin-Jimenez D, et al. Effect of Dupilumab in CRSwNP Sinonasal Outcomes from Real Life Studies: A Systematic Review with Meta-analysis. Curr Allergy Asthma Rep. 2025;25(1):13. Published 2025 Feb 5. doi:10.1007/s11882-025-01192-y.